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Published on: May 16, 2020
Molecular and clinical characterization of PTPN2 expression from RNA-seq data of 996 brain gliomas
Peng-Fei Wang1, Hong-Qing Cai1,2, Chuan-Bao Zhang3,4,5
1Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Building 1, Ward 6, Xiang Shan Yi Ke Song Road 50, Haidian, Beijing, China.
Background:
Immune checkpoint inhibitors have been shown to promote antitumor immunity and achieve durable tumor remissions. However, certain tumors are refractory to current immunotherapy. These negative results encouraged us to uncover other therapeutic targets and strategies. PTPN2 (protein tyrosine phosphatase, non-receptor type 2) has been newly identified as an immunotherapy target. Loss of PTPN2 sensitizes the tumor to immunotherapy via IFNγ signaling.
Methods:
Here, we investigated the relationship between PTPN2 mRNA levels and clinical characteristics in gliomas. RNA-seq data of a cohort of 325 patients with glioma were available from the Chinese Glioma Genome Atlas and 671 from The Cancer Genome Atlas. R language, GraphPad Prism 5, and SPSS 22.0 were used to analyze data and draw figures.
Results:
PTPN2 transcript levels increased significantly with higher grades of glioma and in isocitrate dehydrogenase (IDH) wild-type and mesenchymal subtype gliomas. A comprehensive biological analysis was conducted, which indicated a crucial role of PTPN2 in the immune and inflammation responses in gliomas. Specifically, PTPN2 was positively associated with HCK, LCK, MHC II, and STAT1 but negatively related to IgG and interferon. Moreover, canonical correlation analysis showed a positive correlation of PTPN2 with infiltrating immune cells, such as macrophages, neutrophils, and CD8+ T cells. Clinically, higher levels of PTPN2 were associated with a worse overall survival both in patients with gliomas and glioblastomas.
Conclusion:
PTPN2 expression level was increased in glioblastomas and associated with gliomas of the IDH wild-type and mesenchymal subtype. There was a close correlation between PTPN2 and the immune response and inflammatory activity in gliomas. Our results show that PTPN2 is a promising immunotherapy target and may provide additional treatment strategies.
Insights
Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is elevated in high-grade gliomas and linked to poor survival. Targeting PTPN2 may enhance immunotherapy efficacy for brain tumors.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Molecular Biology
Background:
- Immune checkpoint inhibitors (ICIs) show promise but face resistance in certain tumors.
- Protein tyrosine phosphatase, non-receptor type 2 (PTPN2) is a novel immunotherapy target.
- PTPN2 inhibition sensitizes tumors to immunotherapy via interferon-gamma (IFNγ) signaling.
Purpose of the Study:
- Investigate the association between PTPN2 mRNA levels and glioma clinical characteristics.
- Determine PTPN2's role in glioma immune and inflammatory responses.
- Evaluate PTPN2 as a potential immunotherapy target in gliomas.
Main Methods:
- Analyzed RNA-seq data from 325 Chinese Glioma Genome Atlas and 671 The Cancer Genome Atlas glioma patients.
- Utilized R language, GraphPad Prism 5, and SPSS 22.0 for data analysis.
- Conducted comprehensive biological and canonical correlation analyses.
Main Results:
- PTPN2 mRNA levels significantly correlated with higher glioma grade, IDH wild-type, and mesenchymal subtype.
- PTPN2 positively associated with immune markers (HCK, LCK, MHC II, STAT1) and infiltrating immune cells (macrophages, neutrophils, CD8+ T cells).
- Higher PTPN2 levels correlated with worse overall survival in glioma and glioblastoma patients.
Conclusions:
- PTPN2 expression is elevated in glioblastomas, particularly IDH wild-type and mesenchymal subtypes.
- PTPN2 is closely linked to immune response and inflammation in gliomas.
- PTPN2 represents a promising target for novel glioma immunotherapy strategies.
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